Synthesis and experimental study of norfloxacin labeled with technecium-99m as a potential agent for infection imaging

Introduction: Differentiation between infection and sterile inflammation is one of the most difficult medical problems and is relevant in many clinical situations. Scintigraphy with radiolabeled antibiotics, especially labeled fluoroquinolones, is a promising tool for diagnosing bacterial inflammation. We have attempted to synthesize ^99mTc-norfloxacin and studied its properties in experiment. Methods: In present study we labeled norfloxacin with 99mTc, determined its radiochemical purity by thin-layer chromatography procedure, compared the bactericidal activity of ^99mTc-norfloxacin and unlabelled norfloxacin by disk diffusion, performed in vitro binding assays and evaluated the feasibility of ^99mTc-norfloxacin to image soft-tissue infections in rat modal of thigh muscle infection. Scintigraphy was performed at 30 min, 90 min and 18 h post injection. Abscess -to-normal-site ratios were calculated. Results: In this study ^99mTc-norfloxacin with high radiochemical purity and low colloid content was synthesized. Disk diffusion method showed that ^99mTc-norfloxacin retains bactericidal properties of unlabelled norfloxacin. In vitro binding studies demonstrated small degree of the tracer binding with S. aureus and ability of ^99mTc-norfloxacin to bind with killed as well as alive bacteria. Uptake of the tracer was clearly visible in infected muscles and not visible in sterile inflammed muscles. Conclusion: The ^99mTc-norfloxacin retains bactericidal properties of unlabelled norfloxacin. The tracer demonstrated small degree of S. aureus binding both with killed as well as alive bacteria. Studies which were performed in vivo in rats with a model of thigh muscle infection showed good ability of the radiopharmaceutical to image the infection.